FAILURE OF COMPLETE SUPPRESSION OF ENDOGENOUS GLUCOSE-PRODUCTION BY EUGLYCEMIC HYPERINSULINEMIA IN NORMAL HUMANS

In normal subjects, endogenous glucose production (EGP) is usually ass umed to be completely suppressed during euglycaemic clamp studies perf ormed at high insulin levels (> 100 mU L(-1)). However, this assumptio n is based on non-steady-state tracer measurements of EGP which are pr one to negative errors. We have used purified [6-(3) H]glucose in an o ptimal tracer infusion protocol to assess the suppression of EGP durin g 3 h euglycaemic clamps in eight normal men. An insulin infusion rate of 5 mU kg(-1) min(-1) was chosen to achieve supraphysiological (>500 mU L(-1)) plasma insulin concentrations. Using a labelled exogenous g lucose infusion, plasma glucose (mean +/- SEM 5.3 +/- 0.1 mmol L(-1)) and glucose specific activities (mean 100 +/- 3% of basal) were mainta ined constant from 80 to 240 min. During hyperinsulinaemia, isotopical ly determined glucose appearance rates (Ra) were greater than glucose infusion rates (GIR) throughout the euglycaemic clamp period (P < 0.00 1) and EGP (Ra-GIR) was always greater than zero. In seven of the eigh t; subjects studied EGP was partly suppressed but showed a wide variat ion (EGP 5 to 91% of basal at 80-120 min and 12 to 87% of basal at 200 -240 min) while in one subject EGP rose above basal (by 72% at 80-120 min and 49% at 200-240 min). We conclude that EGP is not completely su ppressed during euglycaemic clamps at high insulin levels.